Hepatitis B Vaccine Derived Protection in The
Gambia: Epidemiological Perspective
Hilton Whittle, Maimuna Mendy,
Ingrid Peterson,David Jefferies, Tom Peto, Marianne van der Sande,
Sophie Moore and Andy Hall
THE WEST AFRICAN PROBLEM
CIRRHOSIS
25% carriers
die of
liver failure
or
liver cancer
Chronic Hep B
(15% adults
Aflatoxin
Exposure
(100%)
Chronic Hep C
(3-5% adults)
1975 200519951985
1983/4 introduction
of HBV
immunisationSurvey points
2008 survey
HBV surveys in Keneba and Manduar
MANDUAR
The team
HBV s antigen status No. children positive %
Mother +/ father –
Mother -/ father +
Mother -/ father –
Older sib +
Older sib -
28/99
12/25
51/345
35/83
24/241
28.2
26.6
14.7
42.2
9.9
Proportion of HBsAg positive children in 1980
in relation to serostatus of parents in 1973
Effect of vaccination on Hep B infection in two Gambian villages (Whittle,2003)
Whittle, 1989
Viral load in HBV carriers.
Decrease in levels of antibody to anti-HBs with time since vaccination, by peak anti-body response (Van der Sande 2003).
Breakthrough infection. K and M, 2008.
Vaccine efficacy (95%CI) against HBV Infection
and Carriage in Keneba and Manduar 2008.
Age (years) infection carriage
1-4 84.8 (80.2, 85.3) 97.7 (84.1, 99.7)
5-9 96.2 (92.1, 98.2) 96.7 (87.0, 99.2)
10-14 92.0 (87.7, 94.8) 93.2 (82.1, 97.4)
15-19 90.8 (85.9, 94.0) 98.1 (86.9, 99.7)
20-24 75.3 (68.3, 80.8) 96.0 (84.0, 99.0)
25-29 58.2 (47.5, 66.7) 89.3 (67.3, 96.5)
all 82.9 (80.2, 85.3) 97.7 (84.1, 99.7)
Whittle, 2002
Relative risk ( 95% C.I.) of HBV infection or carriage in vaccinated children
infection carriage
Mother HBsAg +/- 2.0 (1.0-3.9 ) +
Mother HBeAg +/s+ 6.9 (2.3-20 ) ++++
Peak antibody <10/>10 11.9 (4.9-28.8 ) 95 (19-466)
HBV infection and marital status. K and M 2008
Phased introduction of hepatitis B vaccination in The Gambia. GHIS(1987)
Risk of infection and probability of core antibody reversion by peak antibody (Jack, 1999).
.
Proportion (95% C.I.) with surface antibody and GMC of participants by infant vaccination and adolescent boosting status (van der Sande; 2007).
Crude and adjusted odds ratios (OR, 95%C1) for short and long term(1year) amnestic response
after boosting.
Vaccine efficacy against Hepatitis B infection and carriage by age in The Gambia ( GHIS data).
% vaccine efficacy (95% C.I.)
Age Infection Carriage
4 years 84 (78-89) 94 (84-98)
9 years 83 (78-87) 94 (84-98)
15 years 66 (57-74) 97 (92-100)
Prevalence HBV carriage by agein The Gambia (Peto ,unpublished)
Age HBsAg- HBsAg+ Percentage Total
1.0-4.9 1,920 1 0.05 1,921
5.0-9.9 1,586 5 0.31 1,591
10.0-14.9 815 10 1.21 825
15.0-18.5 273 3 1.09 276
Total 4,594 19 0.41 4,613
Breakthrough infections
• Do breakthrough infections boost antibody and immunity?
• Do these infections persist to cause occult hepatitis?
• Do genetic factors play a role?
• Who is the source of infection?
• Are they caused by mutant viruses?
Contrasts between in Asia and Gambia
• Higher proportion of e antigen carriers in Asian mothers.
• Fewer breakthrough infections but similar antibody decay in Asians.
• Breakthrough infections by mutant viruses more frequent in Asia.
Immunogenetics
• Response to Hep B vaccine is 77% heritable (Newport,2004).
• Non-response associated with HLA class 2 genes.
• Chronic carriers: susceptibility locus clusterd in class 2 cytokine receptor genes (IFN-AR2 and IL-10RB) on chromosome 21q22 (Frodsham,2006).
• Peak antibody related to polymorphisms in CD44 and CD58 genes which affect IFN gamma expression and T-cell function ( Hennig, 2008, 2010).
Correlates of vaccine induced immunity
• Antibody protects against infection. Related to peak, time after vaccination, sex, genetics.
• Does cellular immunity clear infection and protect against persistence? If so what are the mechanisms?
• Do breakthrough infections enhance immunity or persist to cause damage?
• Details needed of immune response to booster dose of vaccine.
Big questions
• Is a dose of vaccine needed at birth?
• Is a booster dose necessary?
• Are breakthrough infections useful or harmful?
• How is long term immunity maintained after vaccination?
Thank You
• All who helped and encouraged us over the years
• MRC
• The Gambian Government
• International agency for Research on Cancer
